Oral care formulations that enhance amount of soluble zinc

ABSTRACT

An oral care composition and method are described in which the composition includes a film or a plurality of film fragments entrained in a carrier. The film or plurality of film fragments comprises a zinc compound and the carrier comprises a polysaccharide and a maleic anhydride copolymer. The composition and methods provide benefits including one or more of increased consumer acceptability, improved solubility of zinc thus permitting the use of lower amounts of zinc compounds and reducing the adverse astringency associated with zinc, decreased adverse reactions brought about by the presence of zinc ions, enhanced aesthetics, improved stability for active or other functional materials, and controlled delivery of active materials such as zinc.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationSer. No. 61/181,116, filed on 26 May 2009, which is incorporated hereinby reference.

BACKGROUND

This application relates to oral and personal care compositions, andmore particularly to compositions comprising a film entrained in acarrier, in which the film includes an active agent. Such compositionsinclude, for example, dentifrices.

The aesthetic appeal of such compositions is important, and can havesignificant effects on consumer acceptance and usage. Aesthetic effectshave been acknowledged to play an important role in consumer acceptanceof many products. Although such products have met with consumerapproval, the art seeks to further improve the aesthetic effects as wellas the cosmetic and therapeutic benefits of these products. Indeed, manysuch compositions known in the art are deficient in one or moreattributes.

Compositions for enhancing health, hygiene or appearance, such as oralcare compositions, skin care compositions and hair care compositions,are used by millions of people. These compositions are used for a widevariety of purposes, including for enhancing personal health, hygiene,and appearance, as well as for preventing or treating a variety ofdiseases and other conditions in humans and in animals.

The formulation of such compositions presents a number of challenges.They must be pharmaceutically and/or cosmetically acceptable for theirintended use. Compositions that contain therapeutic active materialspreferably deliver the active at effective levels, avoiding unduechemical degradation. Similarly, compositions containing cosmeticallyfunctional materials must deliver the material to, e.g., the oralcavity, skin or hair at effective levels under the conditions that theyare typically used by the consumer.

Water-soluble films for oral administration of therapeutic agents arewell known in the art. It is also known in the art to use such films foradministering a breath freshening agent, e.g., menthol. The known filmsfor administering breath freshening agents and/or active pharmaceuticalagents are generally comprised of at least one water-soluble polymersuitable for human consumption and at least one compound that enhancesthe wettability of the water-soluble polymer, typically selected frompolyalcohols, surfactants and plasticizers. For example, U.S. Pat. No.5,948,430 disclosure of which is incorporated by reference herein in itsentirety, describes a monolayer film that can be adhered to the oralcavity to release a pharmaceutically or cosmetically active ingredient,wherein the film comprises at least one water-soluble polymer; at leastone member selected from the group consisting of a polyalcohol, asurfactant and a plasticizer; at least one cosmetic or pharmaceuticallyactive ingredient; and a flavoring agent.

U.S. Pat. No. 5,700,478, the disclosure of which is incorporated byreference herein in its entirety, describes a laminated device forcontrolled release of a substance within a mucosa-lined body cavityincluding a water-soluble adhesive layer comprised of a water-solublepolymer and a water-soluble plasticizer, and a water-soluble polymerlayer. This patent teaches a multiple layer laminate that dissolvesrelatively slowly for controlled or sustained release of a substance.

U.S. Pat. No. 4,900,552, the disclosure of which is incorporated byreference herein in its entirety, describes a trilaminate film suitablefor prolonged and sustained delivery of an active ingredient in a buccalcavity. The trilaminate includes a hydratable muco-adhesive base layer;a non-adhesive reservoir layer; and a water-impermeable barriersandwiched between and bonded to the base layer and the reservoir layer.This patent discloses slowly disintegrating films for prolonged orsustained release of a substance.

U.S. Pat. No. 5,047,244, the disclosure of which is incorporated byreference herein in its entirety, discloses a therapeutic dosage formcomprising an anhydrous but hydratable monolithic polymer matrix thatcontains amorphous fumed silica as well as a therapeutic agent, and awater-insoluble barrier layer secured to the polymer matrix and defininga non-adhesive face. This patent does not disclose rapidlydisintegrating films, but instead contemplates compositions that arecapable of providing improved availability of therapeutic agents from acontrolled release muco-adhesive carrier system.

U.S. Patent No. 6,669,929, and U.S. Patent Application Publication No.2003/0053962, the disclosures of each of which are incorporated byreference herein in their entirety, disclose film forming agents usefulin oral care compositions. The films dissolve in the mouth and releasefunctional components, typically flavorants.

It is known to incorporate flavorants, colorants, and some activecomponents in films that dissolve in the oral cavity. These films areused either by themselves as breath freshening strips, teeth whiteningstrips, or as polymer flakes dispersed throughout an oral carecomposition. It also is known to incorporate zinc salts in dentifriceformulations. Use of various zinc salts often is limited by thesolubility of the zinc, undesirable consumer astringency when higherlevels of zinc are utilized, and the reactivity of the zinc once zincions are available for reaction (i.e., the zinc ions sometimes causeadverse reactions within the formulation).

Thus, there is an ongoing need for new oral and personal carecompositions, and methods of their use.

SUMMARY

The present invention provides, in various embodiments, oral andpersonal care compositions comprising a film entrained in a carrier, inwhich the film includes an active agent. In one embodiment, the film isprovided as a plurality of film fragments. In various embodiments, thepresent invention provides compositions comprising a plurality oflamellar fragments in a carrier.

In one embodiment, the oral care composition comprises a film entrainedin a carrier, a zinc-containing compound contained in the film, apolysaccharide, and a maleic anhydride copolymer. In a preferredembodiment, the oral care composition is in the form of a dentifrice.

The embodiments also provide methods for administering a zinc compoundto a human or animal subject in need thereof, the method includingtopically applying to the subject an oral care composition comprising afilm entrained in a carrier, a zinc-containing compound contained in thefilm, a polysaccharide, and a maleic anhydride copolymer. In variousmethods, such methods further comprise disrupting the film after thetopical application.

Compositions and methods of this invention afford benefits overcompositions and methods among those known in the art. Such benefitsinclude one or more of increased consumer acceptability, improvedsolubility of zinc thus permitting the use of lower amounts of zinccompounds and reducing the adverse astringency associated with zinc,decreased adverse reactions brought about by the presence of zinc ions,enhanced aesthetics, improved stability for active or other functionalmaterials, and controlled delivery of active materials such as zinc.Further benefits and embodiments of the present invention are apparentfrom the description set forth herein.

DESCRIPTION

The present invention provides compositions and methods, foradministration to, or use with, a human or other animal subject.Preferably, specific materials and compositions to be used in thisinvention are, accordingly, pharmaceutically- orcosmetically-acceptable. As used herein, such a “pharmaceuticallyacceptable” or “cosmetically acceptable” component is one that issuitable for use with humans and/or animals to provide the desiredtherapeutic, sensory, decorative, or cosmetic benefit without undueadverse side effects (such as toxicity, astringent taste, irritation,and allergic response) commensurate with a reasonable benefit/riskratio. The following definitions and non-limiting guidelines must beconsidered in reading and interpreting the description of this inventionset forth herein.

The headings (such as “Introduction” and “Summary,”) used herein areintended only for general organization of topics within the disclosureof the invention, and are not intended to limit the disclosure of theinvention or any aspect thereof. In particular, subject matter disclosedin the “Introduction” may include aspects of technology within the scopeof the invention, and may not constitute a recitation of prior art.Subject matter disclosed in the “Summary” is not an exhaustive orcomplete disclosure of the entire scope of the invention or anyembodiments thereof.

The citation of references herein does not constitute an admission thatthose references are prior art or have any relevance to thepatentability of the invention disclosed herein. All references cited inthe Description section of this specification are hereby incorporated byreference in their entirety.

The description and specific examples, while indicating embodiments ofthe invention, are intended for purposes of illustration only and arenot intended to limit the scope of the invention. Recitation of multipleembodiments having stated features is not intended to exclude otherembodiments having additional features, or other embodimentsincorporating different combinations of the stated features. SpecificExamples are provided for illustrative purposes of how to make, use andpractice the compositions and methods of this invention and, unlessexplicitly stated to recite activities that have been done (i.e., usingthe past tense), are not intended to be a representation that givenembodiments of this invention have, or have not, been performed.

As used herein, the words “preferred” and “preferably” refer toembodiments of the invention that afford certain benefits, under certaincircumstances. However, other embodiments may also be preferred, underthe same or other circumstances. Furthermore, the recitation of one ormore preferred embodiments does not imply that other embodiments are notuseful, and is not intended to exclude other embodiments from the scopeof the invention. As used herein, the word “include,” and its variants,is intended to be non-limiting, such that recitation of items in a listis not to the exclusion of other like items that may also be useful inthe materials, compositions, devices, and methods of this invention. Ina similar manner, the description of certain advantages or disadvantagesof known materials and methods is not intended to limit the scope of theembodiments to their exclusion. Indeed, certain embodiments may includeone or more known materials or methods, without suffering from thedisadvantages discussed herein.

As used herein, the term “comprising” means that other steps and othercomponents that do not affect the end result may be utilized. The term“comprising” encompasses the expressions “consisting of,” and“consisting essentially of.” The expression “effective amount,” as usedherein denotes an amount of a compound or composition sufficient tosignificantly induce a positive benefit, preferably an oral healthbenefit, but low enough to avoid serious side effects, i.e., to providea reasonable benefit to risk ratio, within the sound judgment of aperson having ordinary skill in the art. The use of singular identifierssuch as “the,” “a,” or “an” is not intended to be limiting solely to theuse of a single component, but may include multiple components.

The oral care compositions of the various embodiments preferably are inthe form of a dentifrice. The term “dentifrice” as used throughout thisdescription, denotes a paste, gel, or liquid formulation. The dentifricemay be in any desired form, such as deep striped, surface striped,multi-layered, having a gel surround the paste, or any combinationsthereof. The film contained in the oral care composition may be of anydesired shape or structure, including multiple small strips, or onecontinuous strip.

The expressions “carrier” or “aqueous carrier” as used throughout thisdescription denote any safe and effective materials for use herein. Suchmaterials include, for example, thickening agents, humectants, ionicactive ingredients, buffering agents, anticalculus agents, abrasivepolishing materials, peroxide sources, alkali metal bicarbonate salts,surfactants, titanium dioxide, coloring agents, flavor systems,sweetening agents, antimicrobial agents, herbal agents, desensitizingagents, stain reducing agents, and mixtures thereof.

All percentages and ratios used herein are by weight of the oral carecomposition, unless otherwise specified. All measurements are made at25° C., unless otherwise specified.

The present invention provides oral or personal care compositionscomprising a film entrained in a carrier, wherein the film comprises azinc compound. As referred to herein, an “oral or personal carecomposition” is any composition that is suitable for administration orapplication to a human or animal subject for enhancing the health,hygiene or appearance of the subject, including the prevention ortreatment of any physiologic condition or disorder, and providingsensory, decorative or cosmetic benefits and combinations thereof.Compositions among those provided herein include oral care compositions,skin care compositions, hair care composition, topical pharmaceuticalcompositions, and ocular compositions. By “oral care composition” asused herein is meant a composition for which the intended use caninclude oral care, oral hygiene, or oral appearance, or for which theintended method of use can comprise administration to the oral cavity.By “skin care composition” as used herein is meant a composition forwhich the intended use can include promotion or improvement of health,cleanliness, odor, appearance, or attractiveness of skin.

Embodiments of this invention comprise a film. As referred to herein, a“film” is a material having a substantially lamellar structure. A“lamellar” structure has, or is capable of having, a size in one or twodimensions (e.g., the x- or y-dimensions) that is substantially greaterthan the thickness of the structure in a third dimension (e.g., thez-direction). Lamellar structures among those useful herein includethose that are substantially planar, layered, or lamelliform. In oneembodiment, the lamellar structure is substantially planar, having asize in both the x- and y-dimensions that is substantially greater thanthe z- direction. In other embodiments, the lamellar structure isnon-planar. In one embodiment, a film of this intention comprises asubstantially continuous surface that can appear as a substantially flatsurface, although in some embodiments the film is deformed. In suchembodiments, the film can have any of a number of shapes, includinghaving a smooth curved surface.

Films among those useful herein may be rigid or plastic, comprising anyof a variety of materials, including materials selected from the groupconsisting of film forming materials, clays, waxes, and mixturesthereof. In one embodiment, the film comprises a film forming polymer.Film forming polymers among those useful herein include materialsselected from the group consisting of water soluble polymers, waterdispersible polymers, water insoluble polymers, and mixtures thereof.

In some embodiments, a film comprises at least one film formingmaterial. In certain embodiments, a film forming material is a polymer.Polymers useful herein include hydrophilic polymers and hydrophobicpolymers. In certain embodiments, the polymer is a water solublepolymer. In some embodiments, the polymer is a water soluble, breakablepolymer that dissolves during use, such as, for example, duringtoothbrushing. The dissolution can occur as a result of, for example,shearing and/or exposure to a solvent comprising a high concentration ofwater, such as saliva. In some embodiments, the polymer is insoluble butbreakable in water by being dispersible, i.e., the polymer breaks downinto small fragments, for example, as a result of shearing. In someembodiments, a polymer is insoluble but swellable. In configurations inwhich a polymer does not break down during use, the polymer can be awater-repellant polymer or an aqueous-stable hydrophilic polymer such ascertain types of cellulose, for example paper. In some embodiments, afilm fragment can comprise a mixture of film forming materials.

Water soluble polymers among those useful herein include celluloseethers, methacrylates, polyvinylpyrollidone, and mixtures thereof. Inone embodiment, the polymer is a cellulose ether, including thoseselected from the group consisting of hydroxyalkyl cellulose polymerssuch as hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose,hyrdoxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, andmixtures thereof. Other polymers among those useful herein includepolyvinylpyrrolidone, cross-linked polyvinyl pyrrolidone,polyvinylpyrrolidone-vinyl acetate copolymer, polyvinylalcohol,polyacrylic acid, poly acrylate polymer, cross-linked polyacrylatepolymer, cross-linked polyacrylic acid (e.g, Carbopol®), polyethyleneoxide, polyethylene glycol, poly vinyl alkyl ether-maleic acid copolymer(such as Gantrez®) and carboxy vinyl polymer; natural gums such assodium alginate, carrageenan, xantham gum, gum acacia, arabic gum, guargum, pullulan, agar, chitin, chitosan, pectin, karaya gum, zein,hordein, gliadin, locust bean gum, tragacantha and otherpolysaccharides; starches such as maltodextrin, amylose, high amylosestarch, corn starch, potato starch, rice starch, tapioca starch, peastarch, sweet potato starch, barley starch, wheat starch, waxy cornstarch, modified starch (e.g. hydroxypropylated high amylose starch),dextrin, levan, elsinan and gluten; and proteins such as collagen, wheyprotein isolate, casein, milk protein, soy protein and gelatin.

Non-limiting examples of water dispersable and swellable polymersinclude modified starch, alginate esters, divalent or multivalent ionsalts of alginates. Non-limiting examples of water insoluble polymersinclude polymers soluble in at least one organic solvent, such ascellulose acetate, cellulose nitrate, ethylene-vinyl acetate copolymers,vinyl acetate homopolymer, ethyl cellulose, butyl cellulose, isopropylcellulose, shellac, silicone polymer (e.g. dimethylsilicone), PMMA (polymethyl methacrylate), cellulose acetate phthalate and natural orsynthetic rubber; polymers insoluble in organic solvents, such ascellulose, polyethylene, polypropylene, polyesters, polyurethane andnylon.

The films useful in the various embodiments can be made in accordancewith the methods described in U.S. Pat. No. 6,669,929, and U.S. PatentApplication Publication No. 2003/0053962, the disclosures of which areincorporated by reference herein in their entirety. The zinc compoundscontained within the film can be incorporated into the film during filmmanufacture using techniques known in the art. A person having ordinaryskill in the art will be capable of making the film containing the zinccompound, using the guidelines provided herein.

In various embodiments, the oral care compositions comprise a pluralityof lamellar film fragments entrained in a carrier. In one embodiment,the composition comprises a film, wherein the film comprises lamellarfragments of the film material. In one embodiment, the compositioncomprises a carrier having distributed therein a plurality of lamellarfragments, wherein the fragments comprise a matrix and a functional zinccompound material. In one such embodiment, the matrix comprises a film.Such fragments may be of any of a variety of shapes or forms, includingsemi-solid or solid discrete portions, fragments, particles, flakes, orcombinations thereof In various embodiments, the film comprises a firstplurality of fragments and a second plurality of fragments, wherein thefirst plurality of fragments differ in composition or appearance fromthe second plurality of fragments. Such difference in composition orappearance can be in any aspect of the composition of the fragment(e.g., different film components, different functional material,different formulation colorant), different appearance (e.g., shape,color, texture, refractive index, reflective index), or combinationsthereof.

In various embodiments, the fragments exhibit perceivable contrast withthe carrier. The perceivable contrast can be sensory contrast, such asoptical contrast, tactile contrast, taste contrast, or olfactorycontrast. In some configurations, optical contrast can be colorcontrast, or a difference in refractive index or reflective index. Insome configurations, color contrast can be imparted by one or morecolorants that comprise different components of the composition. Invarious embodiments, the present invention provides compositionscomprising a plurality of film fragments in a carrier, wherein saidfragments are visibly discernable. As referred to herein, “visiblydiscernable” refers to one or more characteristics of a fragment whichcause the fragment to have a different physical appearance, preferablyto the naked eye, relative to the carrier in which the fragment isentrained. Such characteristics include color, opacity, refractiveindex, reflective index, size, shape, and combinations thereof.

In various embodiments, the fragments have a non-random shape. In oneembodiment, a “non-random” shape is a shape which results from amanufacturing process of shaping, cutting, or other forming process bywhich a specific shape is imparted to a fragment. In such embodiments, anon-random shape is distinguished from such shapes that result fromsimple precipitation or grinding of a material. In one embodiment, a“non-random” shape is “repeating,” wherein the composition comprises aplurality of fragments have substantially the same shape. Such repeatingshape may have any of a variety of forms, and may be selected based on avariety of aesthetic or functional criteria. In certain embodiments, theshape of a film fragment can be a recognizable shape. In certainembodiments, a film fragment can comprise a nonrandom shape. Such shapesinclude simple geometric shapes, such as polygons and elliptical shapes,such as triangles, quadrilaterals (such as a square, a rectangle, arhombus), pentagons, hexagons, oval, and circles. In one embodiment, therepeating shape is a square. Repeating shapes include, in otherembodiments, shapes that are representative of figures or animate orinanimate objects, such as stars, hearts, gems, flowers, trees,shamrocks, a letter of an alphabet, numbers, animals, people, and faces.In various embodiments, the composition comprises a single repeatingshape. In other embodiments, the composition comprises a plurality offragments having a plurality of repeating shapes. In one embodiment, thecompositions of the present invention comprise a plurality of first filmfragments having a first repeated shape and a plurality of second filmfragments having a second repeated shape, wherein the first repeatedshape is different from the second repeated shape.

In various embodiments, the size of the fragments is not critical, andmay be determined pursuant to any of a variety of criteria, includingmanufacturing convenience, affect on visual appearance, surface area,affect on texture in the composition, and combinations thereof. In someembodiments, the film fragments can be up to about 1 inch (25.4 mm) inlength in the longest dimension. As referred to herein, “long dimension”is the dimension of a fragment in length or width (i.e., in the x-andy-dimensions, as the fragment is, or is deformed to be in a planarshape) in a dimension substantially perpendicular to the “thickness” orshortest dimension of the fragment (i.e., the z-dimension). It isunderstood that in various embodiments comprising a plurality offragments, the fragments may be present in a range of sizes due to avariety of factors, including random variation in size, manufacturingtolerances, and intentional sizing or mixing of the fragments throughsieving or similar means. As referred to herein, sizes refer to theaverage size of fragments in a given plurality of fragments.

In various embodiments, the fragments are from about 0.2 mm to about 15mm in long dimension. In various embodiments, the long dimension of thefragments is from 0.2 mm to about 10 mm, from about 0.5 mm to about 10mm, from about 0.8 mm to about 8 mm, from about 0.9 mm to about 5 mm,from about 1.0 mm to about 5 mm, or from about 1.5 mm to about 2.5 mm.In some embodiments, the long dimension of the fragments is at leastabout 3 mm, and can be from about 6 mm to about 13 mm. In certainembodiments, a plurality of film fragments are greater than about 600microns in the longest dimension. In certain embodiments, a plurality offilm fragments are greater than about 1 millimeter in the longestdimension.

In various embodiments, the fragments of the present invention have athickness of from about 1 mil (thousandth of an inch, 25.4 microns) toabout 3 mils (76.2 microns). In various embodiments, the fragments havea thickness of less than about 4 mils or less than about 100 microns andfrom about 0.1 mils (2.54 microns) up to about 10 mils (254 microns),from about 0.5 mils (12.7 microns) up to about 5 mils (127 microns),from about 1.4 mils (35.6 microns) to about 2.0 mils (50.8 microns).

In some embodiments, the compositions of the present invention comprisefragments having an aspect ratio of at least about 5:1. As referred toherein, “aspect ratio” of a fragment is the ratio of the diameter of thesmallest imaginary sphere that can enclose the object to the diameter ofthe largest imaginary sphere that can be completely inside the objectand tangent to the surfaces of the object. For example, the aspect ratioof a sphere is 1:1; in another example, the aspect ratio of a cylinderthat is 2 inches (50.8 mm) long and ¼ inch (6.35 mm) in diameter isslightly over 8:1; in yet another example, a film fragment of thepresent invention that is 1 mil (25.4 microns) in thickness, 1 inch(25.4 mm) in length, and 1 inch (25.4 mm) wide has an aspect ratio ofabout 1414:1.

In some embodiments, the compositions of the present invention comprisefragments having an aspect ratio of at least about 10:1. In variousembodiments, the fragments have an aspect ratio of from about 5:1 toabout 10,000:1, from about 5:1 to about 500:1, from about 10:1 to about1,000:1, from about 10:1 to about 100:1, from about 20:1 to about 100:1,or from about 25:1 to about 35:1.

In various embodiments, the film comprises a formulation colorant thatimparts a color to the film, the composition, or both. In variousembodiments, the film fragments contrast with the carrier, and arewhite, black, or of any color that is visible against or contrasts withthe carrier background. Formulation colorants among those useful hereininclude non-toxic water soluble dyes or pigment, such as, for example,metallic oxide “lakes.” In certain embodiments, the colorant is approvedfor incorporation into a food or drug by a regulatory agency, such asFD&C or D&C pigments and dyes approved by the FDA for use in the UnitedStates. Colorants among those useful herein include FD&C Red No. 3(sodium salt of tetraiodofluorescein), Food Red 17, disodium salt of6-hydroxy-5-{(2-methoxy-5-methyl-4-sulphophenyl)azo}-2-naphthalenesulfonicacid, Food Yellow 13, sodium salt of a mixture of the mono anddisulphonic acids of quinophtalone or 2-(2-quinolyl) indanedione, FD&CYellow No. 5 (sodium salt of4-p-sulfophenylazo-1-p-sulfophenyl-5-hydroxypyrazole-3 carboxylic acid),FD&C Yellow No. 6 (sodium salt ofp-sulfophenylazo-B-naphtol-6-monosulfonate), FD&C Green No. 3 (disodiumsalt of4-{[4-(N-ethyl-p-sulfobenzylamino)-phenyl]-(4-hydroxy-2-sulfoniumphenyl)-methylene}-[1-(N-ethyl-N-p-sulfobenzyl)-A-3,5-cyclohexadienimine],FD&C Blue No. 1 (disodium salt ofdibenzyldiethyl-diaminotriphenylcarbinol trisulfonic acid anhydrite),FD&C Blue No. 2(sodium salt of disulfonic acid of indigotin), andmixtures thereof in various proportions. In one embodiment, the colorantcomprises a water insoluble inorganic pigment, such as titanium dioxide,chromium oxide green, phthalocyanine green, ultramarine blue, ferricoxide, or a water insoluble dye lake. In some embodiments, dye lakesinclude calcium or aluminum salts of an FD&C dye such as FD&C Green #1lake, FD&C Blue #2 lake, D&C Red #30 lake or FD&C # Yellow 15 lake. Incertain embodiments, a water soluble dye, such as, for example, FD&CBlue #1, is contained within a water-insoluble polymer such as, forexample polyethylene such as that found in polyethylene beads (e.g.,Microblue Spectrabeads, sold by Micropowders, Inc.). In certainembodiments, the film comprises a dye such as D&C Red #30. In certainembodiments, a white colorant is used, for example titanium dioxide(TiO₂), titanium dioxide coated mica (e.g., Timiron), a mineral, or aclay. In certain embodiments, the colorant is a non-bleeding dye. Invarious embodiments, the film comprises a colorant at a level of fromabout from 0.5% to about 20% by weight of the film, or from about 1% toabout 15% by weight of the film, or from about 3% to about 12% by weightof the film. In one embodiment, the compositions of the presentinvention comprise a first plurality of film fragments comprising afirst color, and a second plurality of film fragments comprising asecond color. Preferably, the second color is different than the firstcolor.

The film of the present invention, in various embodiments, disintegratesduring use of the composition. In other embodiments, the film does notdisintegrate during use of the composition. In some embodiments, thefilm releases a material, such as the zinc compound, into the carrier.As referred to herein, “disintegrate” refers to physical disruption ofthe film or fragment material, so as to produce a film or film fragmentsof reduced size compared to the original film. Such disruption may bethrough mechanical, chemical, or physical-chemical means. Thedisintegration can result, for example, from shearing, grinding, orexposure to elevated temperatures during use. In various dentifriceembodiments of the present invention, such disintegration results frombrushing of the composition on the teeth of the subject using thecomposition. In one embodiment, the film disintegrates so as to releasea functional material (as further described herein). In someembodiments, a film fragment can disintegrate into small pieces that arenot visually discernable. In some embodiments, the film fragmentsdisintegrate to collectively form a colloid or gel.

In various embodiments, the film may comprise, in addition to the zinccompound other therapeutic actives. As referred to herein, a therapeuticactive is a material that is useful for the prevention or treatment of aphysiological disorder or condition. Such disorders or conditionsinclude those of the oral cavity (including the teeth and gingiva),skin, hair, and eyes. The specific therapeutic active is preferablydetermined according to the desired utility of the composition. Suchactives include the following.

-   A. antimicrobial agents, such as triclosan, cetyl pyridium chloride,    domiphen bromide, quaternary ammonium salts, sanguinarine,    fluorides, alexidine, octonidine, EDTA, essential oils such as    thymol, methyl salicylate, eucalyptol and menthol, and the like,-   B. non-steroidal anti-inflammatory drugs, such as aspirin,    acetaminophen, ibuprofen, ketoprofen, diflunisal, fenoprofen    calcium, naproxen, tolmetin sodium, indomethacin, and the like,-   C. anti-tussives, such as benzonatate, caramiphen edisylate,    menthol, dextromethorphan hydrobromide, chlophedianol hydrochloride,    and the like,-   D. decongestants, such as pseudoephedrine hydrochloride,    phenylepherine, phenylpropanolamine, pseudoephedrine sulfate, and    the like,-   E. anti-histamines, such as brompheniramine maleate,    chlorpheniramine maleate, carbinoxamine maleate, clemastine    fumarate, dexchlorpheniramine maleate, diphenhydramine    hydrochloride, diphenylpyraline hydrochloride, azatadine meleate,    diphenhydramine citrate, doxylamine succinate, promethazine    hydrochloride, pyrilamine maleate, tripelennamine citrate,    triprolidine hydrochloride, acrivastine, loratadine,    brompheniramine, dexbrompheniramine, and the like,-   F. expectorants, such as guaifenesin, ipecac, potassium iodide,    terpin hydrate, and the like,-   G. anti-diarrheals, such a loperamide, and the like,-   H. H₂-antagonists, such as famotidine, ranitidine, and the like; and-   I. proton pump inhibitors, such as omeprazole, lansoprazole, and the    like,-   J. general nonselective CNS depressants, such as aliphatic alcohols,    barbiturates and the like,-   K. general nonselective CNS stimulants such as caffeine, nicotine,    strychnine, picrotoxin, pentylenetetrazol and the like,-   L. drugs that selectively modify CNS function such as    phenyhydantoin, phenobarbital, primidone, carbamazepine,    ethosuximide, methsuximide, phensuximide, trimethadione, diazepam,    benzodiazepines, phenacemide, pheneturide, acetazolamide, sulthiame,    bromide, and the like,-   M. antiparkinsonism drugs such as levodopa, amantadine and the like,-   N. narcotic-analgesics such as morphine, heroin, hydromorphone,    metopon, oxymorphone, levorphanol, codeine, hydrocodone, xycodone,    nalorphine, naloxone, naltrexone and the like,-   O. analgesic-antipyretics such as salycilates, phenylbutazone,    indomethacin, phenacetin and the like,-   P. psychopharmacological drugs such as chlorpromazine,    methotrimeprazine, haloperidol, clozapine, reserpine, imipramine,    tranylcypromine, phenelzine, lithium and the like.    The amount of medicament that can be used in the films can be    dependent upon the dose needed to provide an effective amount of the    medicament. In a particularly preferred embodiment, triclosan is not    used, and the primary anti-bacterial agent is the zinc compound.

In various embodiments, therapeutic agents useful herein includeanticaries agents, tartar control agents, antiplaque agents, periodontalactives, breath freshening agents, malodour control agents, whiteningagents, antibacterials, steroids, anti-inflammatory agents, vitamins,proteins, conditioning agents, moisturizers, antiperspirant actives,deodorant actives, anesthetics, and mixtures thereof.

In certain oral care embodiments, the film or the oral care compositionmay comprise an oral care active, which is useful for the prevention ortreatment of an oral care disorder or condition. Oral care actives amongthose useful herein include abrasives, anticaries agents, tartar controlagents, antiplaque agents, periodontal actives, breath fresheningagents, malodour control agents, tooth desensitizers, salivarystimulants, whitening agents, and combinations thereof. Active materialsamong those useful herein are described in U.S. Pat. No. 6,596,298,Leung et al.

Tartar control agents among those useful herein include dialkali ortetraalkali metal pyrophosphate salts such as Na₄P₂O₇, K₄P₂O₇,Na₂K₂P₂O₇, Na₂H₂P₂O₇ and K₂H₂P₂O₇; long chain polyphosphates such assodium hexametaphosphate; and cyclic phosphates such as sodiumtrimetaphosphate. In some configurations, a polyphosphate is abeta.-phase calcium pyrophosphate, such as disclosed in U.S. Pat. No.6,241,974, White, Jr. In some embodiments, the film comprises ananticalculus agent at a level of about 15 to 20% by weight of the film.

Odor reducing agents useful herein include sulfur precipitating agents.Such sulfur-precipitating agents include metal salts, such as a coppersalt or a zinc salt. Such salts include copper gluconate, zinc citrateand zinc gluconate. These zinc salts can be used in combination or inaddition to the zinc compounds included in the film. In variousembodiments, the film comprises sulfur precipitating agents at a levelof from about 0.01 to about 30% by weight of film, from about 2% toabout 2.5% by weight of film, or about 10% to about 20% by weight offilm.

In a certain embodiments, the film and/or oral composition may include asaliva stimulating agent (a “succulent”), Such agents include thosedisclosed in U.S. Pat. No. 4,820,506, Kleinberg et al. In someconfigurations, a saliva stimulating agent can include a food acid suchas citric, lactic, malic, succinic, ascorbic, adipic, fumaric andtartaric acids. In various embodiments, the film comprises a salivastimulating agent at a level of from about 0.01 to about 12% by weightof the film, from about 1% to about 10% by weight of the film, or fromabout 2.5% to about 6% by weight of the film. In some embodiments, asaliva stimulating agent can be used in the amelioration of dry mouth.

In certain oral care embodiments, the film comprises other activematerials, such as antibacterial agents such as magnolia extract,triclosan, grapeseed extract, thymol, methyl salicylate, eucalyptol,menthol, hop acids, cetyl pyridinium chloride, (including CPC/Zn andCPC+enzymes) and usnic acid; anti-inflammatory agents such a breathfreshening agents (for example zinc gluconate, zinc citrate, zincchlorite and alpha ionone); tooth desensitizers such as potassiumnitrate, desensitizing polymers, and desensitizing minerals;anti-inflammatory agents such as magnolia extract, ursolic acid; aloe,and cranberry extract; vitamins such as pantheon, retinyl palmitate,folic acid, tocopherol acetate and Vitamin A; herbs or herbal extractssuch as rosemary, oregano, chamomilla recutita, mentha piperita, salviaofficinalis, orcommiphora and myrrha; proteins, such as milk proteinsand enzymes such as peroxide-producing enzymes, amylase,plaque-disrupting agents such as papain, glucoamylase, glucose oxidase,and “next generation” enzymes; whitening agents such as hydrogenperoxide, urea peroxide and phosphate salts; medicinals, such as aspirin(acetyl salicylic acid), caffeine, and benzocaine; probiotics; abrasivessuch as silicas (including high cleaning silica); anti-caries agentssuch as stannous salts (e.g., stannous fluoride) or amino fluoride; anitric oxide synthase inhibitor such as guanidinoethyldisulfide;calcium; antiattachmetn ingredients, such as polyumylphosphonic acid;preservatives such as Solbrol® (Bayer Chemicals AG);silicones;chlorophyll compounds, anti-leukoplakia agents such as beta-carotene;anti-oxidants such as Vitamin E; and combinations thereof. In someembodiments, the films comprise such active materials at a concentrationof about 0.01 to about 30% by weight of film, from about 2% to about 25%by weight of the film, or from about 10% to about 20% by weight of film.

In certain embodiments, the film and/or oral care composition includes apreservative. A preservative can be added in amounts from about 0.001 wt% to about 5 wt %, preferably from about 0.01 wt % to about 1 wt % ofthe film. Non-limiting examples of preservatives include sodium benzoateand potassium sorbate.

In certain embodiments, the entrainment of the zinc compound in the filmmatrix suspended in the dentifrice or other composition isolates theseagents from interaction with reactive ingredients present in thecomposition so that the agents are maintained substantially separatefrom the reactive composition ingredients during manufacture and storagewhile subsequently being released from the film matrix when thecomposition is used. Isolation not only avoids adverse reactions thatmay occur between the zinc compound and other components that arepresent in the carrier material, but also avoids dissolution of the zinccompound and premature release of zinc ions, as well as reducing theastringent taste associated with the use of zinc compounds.

The compositions of the present invention comprise a carrier in which afilm, or fragments, is entrained. As referred to herein, a “carrier” isany material or composition in which a film can be entrained and issuitable for administration or application to the human or animalsubject to whom the composition is administered or applied. As referredto herein, “entrained” refers to the embedding or suspension of a filmin a carrier. In various embodiments comprising a plurality offragments, such fragments may be entrained by embedding, suspension,dispersion or other distribution of the fragments in the carrier. Invarious embodiments, the fragments are distributed substantiallyhomogenously throughout the carrier. In other embodiments, the fragmentsare not distributed homogenously in the carrier. In certain embodiments,the distribution of a plurality of film fragments is substantiallyisotropic within the carrier. Dentifrice compositions that include aplurality of film fragments dispersed or suspended in a carrier arecommercially available under the tradename Max Fresh® or Max White®,from Colgate-Palmolive Company, New York, N.Y.

The film includes a zinc compound that provides a source of zinc ions.Zinc ions have been found to help in the reduction of gingivitis,plaque, sensitivity, and improved breath benefits. Many zinc compounds,however, are sparingly soluble and hence, must be used in relativelylarge amounts to provide an effective amount of zinc ions.Unfortunately, many zinc compounds also have unpleasant consumerastringency, especially when used in relatively high concentration. Thepresent invention provides a mechanism that increases the availabilityof soluble zinc, thus permitting the use of lower concentrations of zinccompounds to achieve the same or more beneficial effect.

The presence of zinc compound in a film allows incorporation of arelatively insoluble compound into a dentifrice. The method of action offilms in dentifrice formulations typically is based on themucoadhesiveness of the film and subsequent retention of the films inthe mouth, as the insolubility of the zinc presumably would limit itsusefulness during the 1-2 minutes of consumer brushing. The presentinventors have found that the incorporation of a zinc compound into afilm, coupled with a polysaccharide and a maleic anhydride copolymersystem, dramatically improves the solubility of the zinc and enables anincrease in the amount of zinc to levels that are commensurate withcurrently marketed zinc citrate formulations, which have been clinicallyproven to have anti-plaque and anti-gingivitis efficacy.

The oral compositions of the preferred embodiments include a zinccompound in a film that provides a source of zinc ions. The zinccompound can be a soluble or sparingly soluble compound of zinc withinorganic or organic counter ions. Examples include the fluoride,chloride, chlorofluoride, acetate, hexafluorozirconate, sulfate,tartrate, gluconate, citrate, lactate, malate, glycinate, pyrophosphate,metaphosphate, oxalate, phosphate, carbonate salts, and oxides of zinc.Preferably, the zinc compound is zinc oxide, and is used as areplacement for conventional anti-bacterial agents such as triclosan.

The amount of zinc compound included in the film can vary from about 20%to about 60% by weight, preferably from about 25% to about 55%, morepreferably from about 30% to about 55%, and most preferably about 50% byweight. The amount of film included in the oral composition also canvary anywhere from about 0.1% to about 5.0%, more preferably from about0.25% to about 3.0%, and most preferably from about 0.5% to about 2.0%by weight film. The amount of zinc compound employed in the overall oralcomposition therefore can vary from about 0.5 to about 2.5 wt %, basedon the total weight of the composition, typically from about 1 to about2 wt %, based on the total weight of the oral care composition.

Zinc ions are derived from the zinc compound present in the film in thedentifrice composition in an effective amount. An effective amount ofzinc ions is defined as from at least 1000 ppm zinc ion, preferably2,000 ppm to 15,000 ppm. More preferably, zinc ions are present in anamount from 3,000 ppm to 13,000 ppm and even more preferably from 4,000ppm to 10,000 ppm. This is the total amount of zinc ions that is presentin the compositions for delivery to the tooth surface.

Examples of suitable zinc compounds that serve as zinc ion sources arezinc oxide, zinc sulfate, zinc chloride, zinc citrate, zinc lactate,zinc gluconate, zinc malate, zinc tartrate, zinc carbonate, zincphosphate, and other salts listed in U.S. Pat. No. 4,022,880.

The zinc compound can be incorporated into the film using techniquesknown in the art. For example, the zinc compound can be formed in aslurry with the polymer or polymer mixture forming the film, togetherwith additives such as propylene glycol, Polysorbate 80 (Tween 80),water, flavorants, colorants, and the like, and the slurry dried to forma film. Other methods of making the film are known and described in, forexample, U.S. Pat. No. 6,669,929, and U.S. Patent ApplicationPublication No. 2003/0053962, the disclosures of which are incorporatedby reference herein in their entirety. It is preferred that the zinccompound is zinc oxide, and is present in the dried film in an amount ofabout 50% by weight, based on the total weight of the film.

The compositions of the embodiments may be described as comprising twophases, wherein one phase comprises a carrier and a second phasecomprises the aforementioned film or fragment. The term “phase” as usedherein denotes a physical phase as understood in the physical andmaterial sciences, i.e., a portion of a material whose properties andcomposition are uniform. However, a phase as used herein can bediscontinuous, i.e., a phase can comprise a plurality of separatecomponents. For example, a plurality of polymer film fragments ofidentical composition is considered to comprise a single phase. In someembodiments, a film fragment can be entirely embedded within thematerial comprising the first phase, or totally or partially exposed onthe surface of the first phase. For example, if the composition is adentifrice comprising both a gel and film fragments, a film fragment canbe totally surrounded by the gel, or partially or totally exposed on thesurface of the gel. In certain embodiments, compositions comprise morethan two phases. Such multi-phase compositions include those having twocarriers, each of which contributes a phase to the composition, inaddition to film fragments as described herein. Other multi-phasecompositions include those having a single carrier and two or morepluralities of fragments, wherein the pluralities of fragments havediffering compositions.

In various embodiments, the carrier is a liquid, semi-solid or solid. A“liquid” can be a liquid of low or high viscosity. A liquid can be aliquid such that flow is imperceptible under ambient conditions. Forexample, a soap, such as an ordinary bar of hand soap, can be considereda liquid herein. A liquid can be a thixotropic liquid. A “semi-solid” asused herein can be a gel, a colloid, or a gum. As used herein,semi-solids and liquids are fluids distinguished on the basis ofviscosity: a semi-solid is a high viscosity fluid, while a liquid haslower viscosity. There is no definitive dividing line between these twotypes of fluids. A semi-solid can, in certain embodiments, have aviscosity as high as thousands of mPas. Carriers among those usefulherein include liquids, pastes, ointments, and gels, and can betransparent, translucent or opaque.

In certain embodiments, the compositions of the present invention areoral care compositions, suitable for administration to the oral cavity.Such compositions include dentifrices, mouthwashes, dental gels,lozenges, beads, gums, oral strips, mints, liquid toothpastes, sprays,paint-on gels, lip balms, whitening strips, breath strips, oral chews,and combinations thereof. An oral care composition disclosed herein canbe used, for example, for cavity prevention, whitening, plaqueprevention or reduction, gingivitis prevention or reduction, tartarcontrol, sensitivity prevention or reduction, or breath malodorprevention or reduction, and stain prevention.

The specific composition of the carrier preferably depends on theintended use of the composition. In various embodiments, the carrier isaqueous, comprising from about 5% to about 95% water or from about 10%to about 70% water. In other embodiments, the carrier is substantiallynon-aqueous. In a dentifrice carrier, water content can be from about 5%to about 70%, from about 10% to about 50%, or from about 20% to about40%. When the presence of water will cause the film to disintegrate, itis particularly preferred that the dried film contain no free water, inwhich the amount of water is substantially 0%, or negligible.

The carrier may comprise any of a variety of materials, includingemulsifiers, thickeners, fillers, and preservatives. In someembodiments, the carrier may include a functional or active material,such as those described above. In some embodiments, the carriercomprises the same functional material as the film.

In one embodiment, the carrier is suitable for use as a dentifrice. Insome embodiments, the carrier comprises a humectant, such as glycerine,sorbitol or an alkylene glycol such as polyethylene glycol or propyleneglycol. In some configurations, the carrier comprises a humectant at alevel of from about 10% to about 80% by weight, or about 20% to about60% by weight of the composition. Carrier compositions among thoseuseful herein are disclosed in U.S. Pat. Nos. 5,695,746, Garlick, Jr.,et al, and 4,839,157, Mei-King Ng et al.

In various dentifrice embodiments, the carrier comprises thickeners,gelling agents or combinations thereof Thickeners or gelling agentsuseful herein include inorganic, natural or synthetic thickeners orgelling agents. In some configurations, the carrier comprises thethickener and gelling agent at total levels of from about 0.10% to about15% by weight, or from about 0.4% to about 10% by weight of thecomposition. Examples of thickeners and gelling agents useful hereininclude inorganic thickening silicas such as: an amorphous silica, forexample Zeodent® 165 (Huber Corporation); Irish moss; iota-carrageenan;gum tragacanth; or polyvinylpyrrolidone. In certain embodiments, thecarrier comprises a polishing agent, such as a silica, a calcinedalumina, sodium bicarbonate, calcium carbonate, dicalcium phosphate orcalcium pyrophosphate. In various embodiments, the carrier can be avisually clear composition.

In various dentifrice embodiments, comprising a visually clear carrier,the composition comprises at least one polishing agent. Polishing agentsamong those useful herein include collodial silica, such as, forexample, Zeodent® 115 (Huber Corporation), and alkali metalaluminosilicate complexes (i.e., a silica comprising alumina). In someconfigurations, a polishing agent can have a refractive index close tothat of a gelling agent combined with water and/or humectant. In variousembodiments, the carrier comprises the polishing agent at a level offrom about 5% to about 70% by weight of the composition.

In certain dentifrices, the carrier comprises a surfactant or mixture ofsurfactants. Surfactants among those useful herein include water-solublesalts of at least one higher fatty acid monoglyceride monosulfate, suchas the sodium salt of the monsulfated monoglyceride of hydrogenatedcoconut oil fatty acids; cocamidopropyl betaine; a higher alkyl sulfatesuch as sodium lauryl sulfate; an alkyl aryl sulfonate such as sodiumdodecyl benzene sulfonate; a higher alkyl sulfoacetate; sodium laurylsulfoacetate; a higher fatty acid ester of 1,2-dihydroxy propanesulfonate; and a substantially saturated higher aliphatic acyl amides ofa lower aliphatic amino carboxylic acid, such as those having 12 to 16carbons in the fatty acid, alkyl or acyl radicals; and mixtures thereof.Amides can be, for example, N-lauroyl sarcosine, and the sodium,potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, orN-palmitoyl sarcosine. In various embodiments the carrier comprises thesurfactant at a level of from about 0.3% to about 5% by weight ofcomposition, or about 0.5% to about 3% by weight of composition.

The present invention also provides methods for making a dentifricecarrier. In one embodiment, water and at least one humectant aredispersed in a conventional mixer until a first homogeneous gel phase isformed. A polishing agent is added into the first homogeneous gel phase.The first homogeneous gel phase and the polishing agent are mixed untila second homogeneous gel phase is formed. A thickener, flavorant andsurfactants are added to the second homogeneous gel phase. Theseingredients are mixed at high speed under vacuum of about 20 to 100mmHg.

The compositions of the present invention are preferably stable undernormal conditions of storage. As referred to herein, “stable” refers tothe lack of significant adverse effect on one, and preferably all,compositional attributes such as appearance, flavor, rheology, andchemical composition of the composition. Preferably, stability in thepresent compositions includes the compositional and physical stabilityof film (including fragments, if any) in the composition. In variousembodiments a composition comprising a film is stable upon storage atambient temperature for at least about two years. It is understood,however, that in some embodiments, an otherwise stable film candisintegrate during use (as discussed above), for example, duringtoothbrushing using a dentifrice composition.

In certain embodiments, a composition can comprise, in addition to filmfragments as described herein, two or more carriers, each of whichcontributes a phase to the composition. Such a composition can be stableto color bleeding. For example, a composition can include film fragmentsand a striped dentifrice such as that disclosed in U.S. Pat. No.6,315,986, Wong et al. In certain embodiments, the film fragments can beof different color(s) than the stripe(s) for enhanced aesthetic appeal.

The present inventors have found that when using zinc compoundscontained in a film, increasing the amount of film in the overallcomposition (e.g., from about 0.5% to about 2.0% by weight), does notincrease the amount of soluble zinc. For example a film containing about50% by weight zinc present in an amount of about 0.5% by weight based onthe total weight of the composition, provides about 0.07% soluble zinc.In a similar manner, a film containing about 50% by weight zinc presentin an amount of about 2.0% by weight based on the total weight of thecomposition, also provides about 0.07% soluble zinc. The presentinventors found, quite unexpectedly, that use of a combination of apolysaccharide and a maleic anhydride copolymer together with thezinc-containing films, provides a nearly 6-fold increase in the amountof soluble zinc.

Compositions that include zinc compounds, (not included within a film),triclosan, and a polysaccharide are described in, for example, PCTapplication number PCT/US09/39268, filed Apr. 2, 2009, entitled“Dentifrice Composition,” the disclosure of which is incorporated byreference herein in its entirety.

The maleic anhydride copolymer preferably is a Gantrez polymer. Thesepolymers have been described previously as antibacterial enhancingagents. One particularly preferred class of antibacterial enhancingagents includes 1:4 to 4:1 copolymers of maleic anhydride or acid withanother polymerizable ethylenically unsaturated monomer. For example,one typical maleic anhydride copolymer includes a methyl vinylether/maleic anhydride copolymer having a molecular weight (“M.W.”)ranging from 30,000 to abut 5,000,000 g/mole, or from 30,000 to 500,000g/mole. These copolymers are commercially available, for example, underthe trademark Gantrez, including Gantrez AN 139 (M.W. 500,000 g/mole),AN 119 (M.W. 250,000 g/mole); and Gantrez S-97 Pharmaceutical Grade(M.W. 700,000 g/mole), of ISP Corporation. In a preferred embodiment,the maleic anhydride copolymer typically comprises a methyl vinylether/maleic anhydride copolymer having a molecular weight ranging from30,000 to abut 1,000,000 g/mole.

When a maleic anhydride copolymer, such as the Gantrez polymer is used,zinc cations tend to react with certain thickening agents such aspolysaccharides that may be present in the dentifrice formulation, inparticular such thickening agents that are present as hydrocolloids andhave a high concentration of groups, such as carboxylate groups, whichare available to react by cross-linking with zinc cations. Suchreactions tend to form an ionic bridge between the maleic anhydridecopolymer and, for example, any cellulosic polymer present in thedentifrice composition as thickening agent. An unacceptably highviscosity in the bulk formula results from this interaction.

The present inventors have found, however, that the use of a thickeningagent that has a low concentration of reactive groups, for examplecarboxylate groups, such as xanthan gum, either as the sole thickeningagent or as one of a plurality of thickening agents, for the maleicanhydride copolymer system provides fewer sites for chemical interactionbetween the zinc ions and the maleic anhydride copolymer. This in turnallows for the incorporation of higher levels of the zinc salt, e.g.zinc oxide or zinc citrate, than would be possible using otherthickening systems, for example based on carboxymethyl cellulose (CMC)or CMC/Carrageenan formulas, without unacceptable increases inviscosity.

In accordance with the preferred embodiments of the present invention, adentifrice containing a film that entrains a zinc compound can beformulated to provide two actives having different and complementarymethods of action, and this can be achieved by use of a dentifrice gumsystem that includes, either wholly, or partly, xanthan gum. Thedentifrice can employ high levels of the zinc active, for example byusing zinc oxide at a relatively high level of from 1 to 2% by weight,based on the weight of the composition, without detrimental effects tothe product aesthetics as a result of an unacceptable increase inviscosity. A particularly preferred amount of zinc citrate for useagainst plaque and gingivitis is 2% by weight, based on the weight ofthe composition.

Without wishing to be bound by any theory of operation, the presentinventors believe that any compatibility between zinc cations and amaleic anhydride copolymer system is significantly reduced when certainhydrocolloids are also present in the composition. This is due to ionicbridging occurring between the maleic anhydride copolymer and thehydrocolloid, which is facilitated by the divalent cationic nature ofthe zinc cations. Carboxymethyl cellulose (CMC), which is such ahydrocolloid employed as a thickener, is especially prone to thisbinding due to the amount and nature of the substituted groups along thebackbone. In order to use zinc in the presence of triclosan and maleicanhydride copolymer, such as the Gantrez product, this reactionpreferably is removed or limited.

Both CMC and xanthan gum contain carboxylate groups along theirbackbones. While both materials are charged polysaccharides, the densityof charged carboxylate groups along the backbone is quite different, andmuch higher for the CMC than for the xanthan gum. For example, one knowncommercially available CMC, CMC 2000S (available from CPKelco) has adegree of substitution of ˜0.9 carboxylate groups per sugar residue.Xanthan gum, in comparison, has a degree of substitution of <0.4carboxylate groups per sugar residue. The number of carboxylate groupsassociated with the chain is important to the theological properties ofa mixture that contains divalent ions such as Zn²⁺ due to the fact thatthese ions complex with the carboxylate groups to form ionic crosslinksor bridges, with the zinc ions crosslinked to two opposing carboxylategroups.

These linkages can be formed from not only carboxylate groups found onCMC, but also sulfate groups found in other thickening agents such asi-Carrageenan. Such linkages can lead to interchain association ofchains and the formation of large networks that can act to dramaticallyincrease viscosity or solubility of the polymer species.

In part, the present inventors have found that a substitution of xanthanfor CMC in a dentifrice can reduce the number of ionic linkagesavailable for network formation, in turn leading to a decrease informula viscosity, exhibited as composition thickness, while maintainingsimilar rheological character of the dentifrice incorporating the CMCgum system. Alternatively, in another embodiment, the use ofhydroxyethyl cellulose (HEC), an uncharged water soluble cellulosederivative can remove all potential for ionic bridging and can producedentifrice formulations of comparable thickness regardless of thepresence of Zn²⁺ cations.

In certain embodiments, the polysaccharide thickening agent has at most0.5 charged groups per sugar residue unit along the polysaccharidebackbone. For further information, see PCT Application No.PCT/US2009/039268, filed on 2 Apr. 2009, which is incorporated herein byreference.

The polysaccharide useful in the embodiments described herein thereforepreferably comprises at least one of xanthan gum and hydroxyethylcellulose. The polysaccharide thickening agent typically consists of atleast one of xanthan gum and hydroxyethyl cellulose. Preferably, thepolysaccharide thickening agent consists of xanthan gum which is presentin an amount of from 0.1 to 1.5 wt % based on the weight of thecomposition, preferably from 0.5 to 1 wt % of the composition.

The dentifrice composition conventionally includes thickening agentsthat provide the dentifrice with the required rheological properties, sothat the dentifrice can be stored in a dispensing container over aperiod of time and thereafter reliably dispensed therefrom by the user.The dentifrice preferably should have the correct viscosity not only tobe dispensed but also to exhibit an acceptable consistency within themouth during tooth brushing. Typical thickening agents include modifiedcelluloses, such as carboxymethyl cellulose (CMC), and otherpolysaccharide or gum components.

The polysaccharide thickening agent may comprise at least one of xanthangum and hydroxyethyl cellulose. The polysaccharide thickening agenttypically consists of at least one of xanthan gum and hydroxyethylcellulose. Preferably, the polysaccharide thickening agent consists ofxanthan gum which is present in an amount of from 0.1 to 1.5 wt % basedon the weight of the composition, preferably from 0.5 to 1 wt % of thecomposition. However, minor amounts of additional thickeners may bepresent, for example carrageenan, gum tragacanth, starch,polyvinylpyrollidione, hydroxyethypropyl cellulose, hydroxybutyl methylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodiumcarboxymethyl cellulose (sodium CMC) and colloidal silica. In oneembodiment, the thickener concentration ranges of 0.1 wt. % to 5 wt. %based on the weight of the composition. In another embodiment, thethickener concentration ranges of 0.5 wt. % to 2 wt. % based on theweight of the composition.

In certain embodiments, an amount of polysaccharide thickeningagent/maleic anhydride copolymer in the oral care composition is 0.5% to5% by weight.

In some embodiments, a pyrophosphate material also is included in thecarrier. The pyrophosphate material may be a sodium pyrophosphate or atetrasodium pyrophosphate material (TSPP).

The present inventors have found that the combination of thepolysaccharide thickening agent and the maleic anhydride copolymersystem unexpectedly and dramatically increases the solubility of thezinc present in the film. This permits the use of a zinc source in anamount that does not create problems with consumer astringency, while atthe same provides increased therapeutic and fresh breath benefits. Therelatively inert polysaccharide thickening agent and maleic anhydridecopolymer system also is not believed to disrupt the stability of thezinc-containing film in the product during normal productshelf-life/use.

The embodiments also provides processes for making compositionscomprising a film entrained in a carrier. In various embodiments, aplurality of fragments are combined with a carrier. In someconfigurations, a carrier and a plurality of film fragments can bemixed. In some configurations, the mixing can comprise slow stirring. Inone preferred embodiment, the process for making the compositioncomprising a carrier having distributed therein a plurality of lamellarfragments includes:

-   (a) providing the carrier including a polysaccharide thickening    agent and a maleic anhydride copolymer;-   (b) adding lamellar fragments of a film containing a zinc compound    to the carrier to form a mixture; and-   (c) homogenizing the mixture.

The term “homogenizing” as used herein refers to the admixture of thefragments and the carrier so as to attain a substantially homogeneousdistribution of fragments in the carrier. It should be noted, however,that the resulting composition still retains two-phase compositioncharacteristics. Homogenizing may be accomplished using any of a varietyof conventional homegenizers.

In another method, the film is added to a component of the carrier(e.g., to a humectant for a dentifrice). The remainder of the carrierthen may be made, and the mixture of film then added to the carrier.

Certain embodiments described herein also provide methods foradministering a zinc compound to a human or animal subject. As referredto herein, “administering” refers to any method by which a compositionis applied on or administered to the subject. In various embodiments,the administration is topical, wherein the composition is applied to anexternal surface of the subject, such as to a surface of the oral cavity(e.g., teeth, gingival, and tongue. The specific route and method ofadministration will depend, of course, on the intended use of thecomposition.

In various embodiments, the present invention provides methods foradministering a functional material to a human or animal subject in needthereof, comprising topically applying to said subject a compositioncomprising a film entrained in a carrier, wherein said film comprisesthe functional material. In one embodiment, the method additionallycomprises disrupting the film after topically applying the film. Suchdisruption may be accomplished by any of a variety of methods, includingchemical and/or mechanical means. Chemical means include degradation ofthe film by contact with water or a material present at the site ofadministration (e.g., saliva in an oral care application). Physicalmeans include agitation, grinding, and shear forces produced byapplication of physical energy to the composition during use (e.g.,brushing in a dentifrice application).

In various embodiments, the present invention provides methods for thetreatment of an oral care condition. As referred to herein, an “oralcare condition” is any disorder or condition which can be prevented ortreated by administration of a composition to the oral cavity, includingdisorders or conditions of the teeth, oral mucosa, gingiva and tongue.Such conditions include caries, gingivitis, periodontitis, and cosmeticconditions such as yellowing and malodour.

The embodiments described herein can be further understood by referenceto the following non-limiting examples.

EXAMPLE 1

This example illustrates, in table 1, how varying the amount of filmcontaining the same amount of zinc compound, (50% by weight), does notincrease the amount of soluble zinc available.

Films were made in accordance with the procedures outlined in U.S. Pat.No. 6,669,929, and U.S. Patent Application Publication No. 2003/0053962,in which the films contained, on a dry weight basis, 50% by weight ofzinc oxide. Films containing 50% by weight zinc oxide can be prepared asdescribed in U.S. Provisional Patent Application No. 61/181,124, filedon 26 May 2009, Attorney Docket No. 8856-00-OC, entitled: “HigherLoading Zinc-Containing Films,” the disclosure of which is incorporatedby reference herein in its entirety. The formula and procedure formaking 50% by weight zinc oxide from application Ser. No. 61/181,124 isreproduced below.

Formula

Slurry Dry Material Supplier Weight % Weight Hydroxypropylmethylcellulose Dow Chemical  6.2  16.8 HPMC E5 Hydroxypropylmethylcellulose Dow Chemical  5.6  15.2 HPMC E50 Zinc Oxide US Zinc 18.7  50.2 (AZO 66USP) Propylene Glycol Univar  5   13.7 Polysorbate 80Croda  0.3  0.8 Menthol  1.2  3.3 Water (DI) — 63  — Total (%) — 100  100  

The slurry is prepared by heating deionized water to about 80° C. Abouthalf of the formula amount of water is added to a beaker. Next, HPMC E5is added and mixed with an overhead mixer until the polymer is wet. HPMCE50 is then added, and the slurry is mixed for 20 min with intermittentscraping of the beaker walls to ensure polymer incorporation. The ZnOpowder is then added along with the remaining amount of water. After 15min of mixing, the propylene glycol and the polysorbate 80 are added.The slurry is complete after an additional 20 min mixing. Air bubbles inthe slurries are removed by mixing with the SpeedMixer™ DAC 150 FVZ for5 min at 1800 rpm. The film is then cast and dried as described in U.S.Pat. No. 6,669,929.

The films then were incorporated into a commercially availabledentifrice known as Max Fresh®, commercially available fromColgate-Palmolive Company, New York, N.Y. The Product listed in thetable below is the Max Fresh product with varying amounts of film (eachfilm containing 50% by weight of zinc oxide), or Max Fresh containing1.0% by weight zinc oxide powder

TABLE 1 Soluble Product Zinc Total Zinc 0.5% film (50% Zn) 0.07% 0.16%1.0% film (50% Zn) 0.06% 0.41% 2.0% film (50% Zn) 0.07% 0.92% 1.0% zincoxide powder 0.07% 0.71%The table shows that soluble zinc levels do not exhibit a dose response(i.e., greater levels of film does not increase soluble zinc levels inthe dentifrice). In addition, the table shows that the zincoxide-containing films do not provide a different level of soluble zincthan a commensurate amount of zinc oxide powder added directly to thedentifrice formulation, without being contained in a film.

EXAMPLE 2

This example illustrates how the addition of xanthan!Gantrez polymersystem (with and without tetrasodium pyrophosphate (TSPP)), dramaticallyincreases the soluble zinc levels over those shown in Table 1 above. Theamount of xanthan/Gantrez polymer used in the carrier portion of theMaxFresh dentifrice base was about 1.95% by weight.

TABLE 2 Product Soluble Zinc Total Zinc 2.0% film (50% zinc oxide) 0.30%1.00% without TSPP 2.0% film (50% zinc oxide) 0.23% 0.90% with TSPP

As shown in Table 2, the use of a xanthan/Gantrez polymer systemincreases the amount of soluble zinc from about 0.07% to about 0.30% or0.23%, given about the same amount of total zinc employed. This amountsto a nearly 4-fold increase in the amount of soluble zinc available.

EXAMPLE 3

This example illustrates, in Table 3, various combinations of zincoxide-containing films, each containing 50% by weight zinc oxide,together with various concentrations of xanthan/Gantrez polymer system(referred to as “Gantrez” in Table 3), and use of TSPP.

TABLE 3 Film Conc. Gantrez Conc. TSPP Soluble Zinc 2   1.95 Yes 0.30%2   1.95 No 0.23% 2   1.5  Yes 0.24% 2   1   Yes 0.18% 2   1.5  No 0.17%2   1   No 0.15% 1   1.95 Yes 0.22% 0.5 1.95 Yes 0.14% 1   1.95 No 0.16%0.5 1.95 No 0.12% 2   0   Yes 0.06%

A response surface analysis indicates that film concentration andGantrez concentration are both factors in determining the soluble zincvalues, with little or no significant interaction terms. Table 3 showsthat, with respect to soluble zinc, 1% or even 0.5% of film can providegreater availability of zinc with the use of the xanthan/Gantrez polymersystem, than a 2% film with no polymer system (bottom comparative valuein Table 3). Indeed, the xanthan/Grantrez polymer system provides nearlya 6-fold increase in available zinc, from 0.05% soluble zinc when nopolymer system was utilized, to 0.30% soluble zinc when the polymersystem was utilized.

The examples and other embodiments described herein are exemplary andnot intended to be limiting in describing the full scope of compositionsand methods of this invention. Equivalent changes, modifications andvariations of specific embodiments, materials, compositions and methodsmay be made within the scope of the present invention, withsubstantially similar results.

What is claimed is:
 1. An oral care composition comprising a filmentrained in a carrier, a zinc-containing compound contained in thefilm, a polysaccharide thickening agent, and a maleic anhydridecopolymer.
 2. The oral care composition of claim 1, wherein the film ispresent in an amount of 0.1% to 5% by weight of the composition.
 3. Theoral care composition of any preceding claim, wherein the film contains20% to 60% by weight of the zinc-containing compound.
 4. The oral carecomposition of any preceding claim, wherein the zinc-containing compoundis at least one zinc containing compound chosen from zinc oxide, zincsulfate, zinc chloride, zinc citrate, zinc lactate, zinc gluconate, zincmalate, zinc tartrate, zinc carbonate, zinc phosphate, and mixturesthereof.
 5. The oral care composition of any preceding claim, whereinthe zinc-containing compound comprises zinc oxide.
 6. The oral carecomposition of any preceding claim further comprising zinc in an amountof 0.5 to 2.5 wt % based on the total weight of the composition.
 7. Theoral care composition of any preceding claim, wherein the film comprisesa combination of two different molecular weights of hydroxypropylmethylcellulose.
 8. The oral care composition of any preceding claim,wherein the film further comprises propylene glycol and polysorbate 80.9. The oral care composition of any preceding claim, wherein thepolysaccharide thickening agent has at most 0.5 charged groups per sugarresidue unit along the polysaccharide backbone
 10. The oral carecomposition of any preceding claim, wherein the polysaccharidethickening agent comprises xanthan gum.
 11. The oral care composition ofany preceding claim, wherein the maleic anhydride copolymer comprises amethyl vinyl ether/maleic anhydride copolymer having a molecular weightof 30,000 to 5,000,000 g/mole.
 12. The oral care composition of anypreceding claim, wherein an amount of polysaccharide thickeningagent/maleic anhydride copolymer in the oral care composition is 0.5% to5% by weight.
 13. The oral care composition of claim 1, wherein a) thefilm comprises a combination of two different molecular weights ofhydroxypropyl methylcellulose, propylene glycol, and polysorbate 80; b)the film contains 20% to 60% by weight of the zinc-containing compound;c) the film is present in an amount of 0.1% to 5% by weight of thecomposition; d) the zinc-containing compound comprises zinc oxide; e)the polysaccharide thickening agent comprises xanthan gum; f) the maleicanhydride copolymer comprises a methyl vinyl ether/maleic anhydridecopolymer having a molecular weight of 30,000 to 5,000,000 g/mole; andg) an amount of polysaccharide thickening agent/maleic anhydridecopolymer in the oral care composition is 0.5% to 5% by weight.
 14. Amethod of making the oral care composition of any preceding claimcomprising: (a) providing the carrier including the polysaccharidethickening agent and the maleic anhydride copolymer; (b) adding lamellarfragments of the film containing the zinc-containing compound to thecarrier to form a mixture; and (c) homogenizing the mixture.
 15. Amethod for administering a zinc compound to a human or animal subject inneed thereof comprising topically applying to the subject an oral carecomposition of any of claims 1-13.
 16. The method of claim 15 furthercomprising disrupting the film after the topical application.